Undifferentiated B-cell lymphomas occur predominantly in children and young adults in a) a geographically delineated form, which is EBV associated, b) a sporadic, widespread form which is not EBV associated, and c) a form arising in certain immunodeficiency syndromes notably that occurring predominantly in homosexual drug abusers, which is also EBV associated. The goals of the present work are to gain information on the epidemiology, pathogenesis and biological differences among the several forms of undifferentiated lymphoma. Links have been established with a number of cancer centers in various parts of the world as part of a concerted effort to characterize, with more precision than has hitherto been achieved, differences in the spectrum of lymphoid neoplasia that occurs in different environments. Biological studies are carried out on cell lines derived from all three of the above categories of undifferentiated lymphomas. Of particular interest is the expression of genes involved in specific chromosomal translocations associated with these tumors, namely the immunoglobulin genes and c-myc oncogene, and changes in the expression of these genes during differentiation of the cell lines. We are interested to determine whether the expression of the translocated c-myc gene is a consequence of the stage of differentiation of the cell. We have derived a number of monoclonal antibodies raised against a Burkitt lymphoma cell line and are currently characterizing these. We hope to find monoclonal antibodies which will be of value in determining the normal counterpart cell of Burkitt's lymphoma. We are also studying the influence of chemotherapeutic agents on the expression of certain cell surface proteins. Methotrexate increases the expression of some proteins, for example HLA, and this phenomenon may be pertinent to therapy with monoclonal antibodies, hormones or other compounds which bind to cell receptors.